N-{2-Fluoro-5-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methyl-acetamide is a potent ligand of γ-Aminobutyric acid A (GABAA) receptors useful in the treatment or prevention of anxiety, epilepsy, sleep disorders, and insomnia, for inducing sedation-hypnosis, anesthesia, and muscle relaxation, and for modulating the necessary time to induce sleep and its duration, such as described in PCT/EP2006/063243 and U.S. 60/692,866.
Throughout the present application the term “compound (I)” refers to N-{2-Fluoro-5-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methyl-acetamide.
Compound (I) is structurally related to N-{3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl}-N-methyl-acetamide, also known as indiplon. The compound and its use as sedative or hypnotic agent is described in U.S. Pat. No. 6,399,621. Unlike compound (I) this compound is only mono-substituted in the phenyl ring.
The only crystalline form of compound (I) is reported to date from the above specifications and shows a melting point of 165-167° C. In the present research this form showed a DSC with a sharp melting peak between 166.2° C. and 167.4° C. The slight difference with the previously reported melting point is acceptable and is within the range of experimental error. This form is coded here Polymorph A.
It is important for a drug substance to be in a form in which it can be conveniently handled and processed. This is of importance, not only from the point of view of obtaining a commercially viable manufacturing process, but also from the point of subsequent manufacture of pharmaceutical formulations comprising the active compound. The drug substance, and compositions containing it, should be capable of being effectively stored over appreciable periods of time, without exhibiting a significant change in the active component's physico-chemical characteristics. Moreover, it is also important to be able to provide drug in a form which is as pure as possible. The skilled person will appreciate that, if a drug can be readily obtained in a stable crystalline form, the above problems may be solved. Therefore, in the manufacture of commercially viable and pharmaceutically acceptable drug compositions, it is desirable, wherever possible, to provide drug in a substantially crystalline, and stable form. Thus, there is a need for a stable crystalline form of compound (I) that can be conveniently handled and processed.